This invention relates generally to cancer diagnosis and therapy, and more specifically, to cancers associated with the Myc oncoprotein Myc is a transcription factor and key cell growth regulator that is frequently deregulated in human malignancy, notably Burkitt""s and T cell lymphomas, where myc genes suffer chromosomal translocation. In colon and lung carcinomas, myc genes are amplified (M. D. Cole, Ann Rev. Genet., 20:361-384 (1986)). Paradoxically, under certain conditions myc can induce apoptosis, a regulated cell suicide process (D. S. Askew et at, Oncogene, 6;1915-1922 (1991); G. I. Evanetal, Cell, 69:119-128 (1992)). However, loss or suppression of apoptosis is an important step in the malignant conversion of human tumors containing deregulated myc oncogenes, including, prominently, prostate carcinoma (T. G. Strohmeyer et al, J. Urol., 151:1479-1497(1994)).
There remains a need in the art for compositions and methods of regulating a deregulated Myc protein and of exploiting and/or diagnosing its apoptotic potential.
In one aspect, the present invention provides mammalian Bin1 nucleic acid sequences and peptides encoded thereby. Currently preferred are alternative splice exons 12A, 12B, 12C and 12D, which are brain-specific splice forms of Bin1 found in malignant cells. The most preferred alternative splice exon is currently Exon 12A
In yet another aspect, the present invention provides a vector comprising a mammalian nucleic acid sequence encoding a Bin1 protein and a host cell transformed by such a vector. Alternatively, this vector may be used in gene therapy applications.
In still another aspect, the invention provides an oligonucleotide probe comprising a nucleic acid sequence as defined herein. Also provided is an antibody raised against a Bin1 protein or peptide thereof.
In yet a further aspect, the present invention provides a diagnostic reagent for breast, prostate, or liver cancer, or deficient Bin1 production, comprising an oligonucleotide probe or an antibody of the invention.
Further provided is a therapeutic reagent comprising a polypeptide, anti-idiotype antibody, or gene therapy vector of the invention.
Still another aspect of the invention provides a method of treating breast, prostate, or liver cancer by administering a therapeutic reagent of the invention.
Other aspects and advantages of the present invention are described further in the following detailed description of the preferred embodiments thereof